The Importance of Interleukin 18, Glutathione Peroxidase, and Selenium Concentration Changes in Acute Pancreatitis

Cytokinemia and oxidative stress are important factors responsible for an inadequate immune response in the early course of acute pancreatitis (AP). The aim of the study was to evaluate the profiles of interleukin 18 (IL-18), glutathione peroxidase (GPx), and selenium concentrations in serum with respect to AP severity and to study the relationships between these parameters and recognized prognostic indicators of AP severity. Prospective clinical analyses were performed on 61 patients with mild and severe forms of AP and for 15 healthy volunteers. In both forms of AP severity, the IL-18 concentration in the serum was significantly higher than in healthy controls. In the severe form of AP, the IL-18 concentration was the highest and exceeded significantly the values recorded on the 1st, 2nd, 3rd, 5th, and 10th days of mild AP. A significantly lower GPx concentration in the serum was recorded in severe AP compared to the mild form and in the control group. There was a significantly lower selenium concentration in the severe form of AP. Significant correlations between GPx and selenium, between IL-18 and GPx, and between IL-18 and selenium were recorded. The ROC analysis shows a high prognostic accuracy of IL-18 and GPx concentrations in the determination of AP severity. IL-18 is released early in the course of AP and may be a key immunomodulator of the inflammatory response in the severe form of this disease. Low GPx and selenium concentrations in severe AP reflect the lower antioxidative ability in this form of AP. IL-18 and GPx may represent new indicators of AP severity.     

Glutathione S-transferase P1 and lung function in patients with alpha1-antitrypsin deficiency and COPD

BACKGROUND: The glutathione S-transferase P1 (GSTP1) gene is involved in detoxification of electrophilic substances of tobacco smoke. A polymorphism at nucleotide 315 of this gene alters its enzymatic activity. OBJECTIVE: We analyzed the association between the variability in the GSTP1 gene and impairment in lung function in smokers with and without alpha(1)-antitrypsin (AAT) deficiency and COPD.Population and method: The study population consisted of 99 patients with smoking-related COPD and 69 patients with AAT deficiency; 198 healthy volunteers provided the frequency of the different polymorphisms in the general population. GSTP1 genotyping was performed by a real-time polymerase chain reaction amplification assay. RESULTS: The frequency (0.28) of the 105Val polymorphism was identical in COPD patients and the general population. However, the frequency was significantly increased (0.44) in patients with AAT deficiency (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.17 to 3.72 compared to control subjects; and OR, 2.41; 95% CI, 1.27 to 4.59 compared to COPD). FEV(1) percentage of predicted was significantly impaired in AAT-deficient carriers of 105Val. This effect was not observed in COPD patients. CONCLUSIONS: These findings suggest that the frequency of the GSTP1 105Val polymorphism is increased in patients with AAT deficiency. Globally, GSTP1 genotypes, age, and tobacco smoking explained 41% of total FEV(1) percentage of predicted variability in patients with AAT deficiency. The modulatory role of GSTP1 in lung disease has only been observed in smokers lacking AAT.     

Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P0.07)but reduced glutathione content was found to be increased significantly(P0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.     

甘草酸二铵联合还原型谷胱甘肽治疗阿维A导致药物性肝损伤疗效观察

目的 探讨甘草酸二铵联合还原型谷胱甘肽治疗阿维A导致药物性肝损伤的疗效。方法 选取2019年1～12月口服阿维A所致药物性肝损伤患者65例,随机分为两组(治疗组32例,对照组33例),其中治疗组给予甘草酸二铵(甘草酸二铵150 mg+10%葡萄糖注射液250 mL,静点每日一次)联合还原型谷胱甘肽(还原型谷胱甘肽1.8 g+10%葡萄糖注射液250 mL,静点每日一次)治疗,2周为一疗程;对照组单独给予还原型谷胱甘肽治疗(用法剂量疗程与治疗组相同)。观察治疗前后两组患者肝功能(ALP、GGT、ALT等)和TG(血脂)的变化,比较两组临床疗效及不良反应。结果 治疗后,两组患者肝功能指标和血脂均有显著改善,治疗组患者肝功能指标和血脂(甘油三酯)改善程度显著优于对照组,差异有统计学意义(P0.05);治疗组治疗总有效率显著高于对照组;两组患者不良反应发生率比较,差异无统计学意义(P0.05)。结论 甘草酸二铵联合还原型谷胱甘肽治疗阿维A导致药物性肝损伤可显著改善患者肝功能并降低血脂,治疗总有效率高、不良反应少,适宜推广应用。     

Acute kidney injury model established by systemic glutathione depletion in mice

Glutathione (GSH) is one of the most extensively studied tripeptides. The roles for GSH in redox signaling, detoxification of xenobiotics and antioxidant defense have been investigated. A drug‐induced rhabdomyolysis mouse model was recently established in L‐buthionine‐(S,R)‐sulfoximine (BSO; a GSH synthesis inhibitor)‐treated normal mice by co‐administration of antibacterial drug and statin. In these models, mild kidney injury was observed in the BSO only‐treated mice. Therefore, in this study, we studied kidney injury in the GSH‐depleted mouse. BSO was intraperitoneally administered twice a day for 7 days to normal mice. The maximum level of plasma creatine phosphokinase (351 487 ± 53 815 U/L) was shown on day 8, and that of aspartate aminotransferase was shown on day 6. Increased levels of blood urea nitrogen, plasma creatinine, urinary kidney injury molecule‐1 and urinary creatinine were observed. An increase of mRNA expression level of renal lipocalin 2/neutrophil gelatinase‐associated lipocalin was observed. Degeneration and necrosis in the skeletal muscle and high concentrations of myoglobin (Mb) in blood (347‐203 925 ng/mL) and urine (2.5‐68 583 ng/mL) with large interindividual variability were shown from day 5 of BSO administration. Mb‐stained regions in the renal tubule and renal cast were histologically observed. In this study, the GSH‐depletion treatment established an acute kidney injury mouse model due to Mb release from the damaged skeletal muscle. This mouse model would be useful for predicting potential acute kidney injury risks in non‐clinical drug development.     

Polymorphism analysis of Glutathione S-transferase A1 in patients with hematological diseases and its effect on GST enzyme activity

Glutathione S-transferases (GSTs) are important drug-metabolizing enzymes that catalyze the binding of glutathione (GSH) to electrophilic substances. GST has genetic polymorphism, and the enzyme activity of GST affects the metabolism of certain drugs in vivo. In the present day, we investigated the GST enzyme activity and GSTA1 gene polymorphism in 170 patients with hematological diseases and explored their relationship. The GSTA1 gene polymorphism of the patient was analyzed by PCR- restriction fragment length polymorphism (PCR-RFLP) technique, and the base sequences of the four mutation sites (-631, -567, -69, and -52) in the promoter region were determined by DNA-Sequencer. The patient's GST enzyme activity was calculated by measuring the rate at which it catalyzed the reaction between 1-chloro-2,4-dinitrobenzene (CDNB) and GSH. The average GST enzyme activities of males and females were 5.20±0.13 and 5.17±0.12 nmol/min/mL, respectively, and the difference was not significant (P = 0.91). The frequencies of genotypes GSTA1*A*A (wild genotype), GSTA1*A*B (heterozygous genotype), and GSTA1*B*B (homozygous mutant genotype) were 75.3%, 22.9%, and 1.8%, respectively. Alleles GSTA1*A and *B were distributed at 86.8% and 13.2%, respectively. The genotype frequency distribution between males and females was no significant difference by Pearson’s chi-square test (P = 0.743). The average GST activity of the heterozygous mutant genotype (4.83±0.76 nmol/min/mL) was lower than the wild genotype (5.34±1.26 nmol/min/mL, P = 0.018), and higher than that of the homozygous mutant genotype (3.32±0.07 nmol/min/mL, P = 0.022). These findings might help us improve the individualized treatment of patients with hematological diseases in the future and promote the development of precision medicine for blood diseases.     

Age related changes in selenium and glutathione levels in different lobes of the rat prostate

Aging represents a major risk factor for prostate cancer; however, mechanisms responsible for this relationship remain unclear. Preclinical and some clinical investigations support the protective role of selenium against prostate cancer possibly through the reduction of oxidative stress. While increased levels of oxidative stress together with decreases in selenium and the major cellular antioxidant glutathione (GSH) are common in tissues of old animals, there is little data available on these parameters in the prostate. In the present study we have compared the levels of selenium, GSH and protein-bound GSH (GSSP) in blood and prostate tissues in young (4-month), mature (12-month), old (18 month), and very old (24 month) male F344 rats. Each prostate lobe (dorsolateral, DL; anterior, AL; ventral, VL) was analyzed separately based upon their differing potential for prostate cancer development. At all ages, selenium levels were lowest in DL相似文献   

Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys

While the mechanisms of cellular aging remain controversial, a leading hypothesis is that mitochondrial oxidative stress and mitochondrial dysfunction play a critical role in this process. Here, we provide data in aging rhesus macaques supporting the hypothesis that increased oxidative stress is a major characteristic of aging and may be responsible for the age-associated increase in mitochondrial dysfunction. We measured mitochondrial DNA (mtDNA) damage by quantitative PCR in liver and peripheral blood mononuclear cells of young, middle age, and old monkeys and show that older monkeys have increases in the number of mtDNA lesions. There was a direct correlation between the amount of mtDNA lesions and age, supporting the role of mtDNA damage in the process of aging. Liver from older monkeys showed significant increases in lipid peroxidation, protein carbonylations and reduced antioxidant enzyme activity. Similarly, peripheral blood mononuclear cells from the middle age group showed increased levels in carbonylated proteins, indicative of high levels of oxidative stress. Together, these results suggest that the aging process is associated with defective mitochondria, where increased production of reactive oxygen species results in extensive damage at the mtDNA and protein levels. This study provides valuable data based on the rhesus macaque model further validating age-related mitochondrial functional decline with increasing age and suggesting that mtDNA damage might be a good biomarker of aging.     

Null genotype of glutathione S-transferase Tl contributes to colorectal cancer risk in the Asian population: a meta-analysis

Background and Aim: Previous studies investigating the association between the glutathione S‐transferase Tl (GSTT1) null genotype and colorectal cancer (CRC) risk in the Asian population have reported controversial results. Thus, a meta‐analysis was performed to clarify the effect of the GSTT1 null genotype on CRC risk in the Asian population. Methods: A comprehensive study was conducted, and 12 case‐control studies were finally included, involving a total of 4517 CRC cases and 6607 controls. Subgroup analyses were performed by the sample size. Results: A meta‐analysis of all 12 studies showed that the GSTT1 null genotype was significantly associated with an increased CRC risk in the Asian population (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.02–1.19, the P‐value of the OR [P_OR] = 0.02, the value of the heterogeneity analysis [I²] = 42%). A more obvious association was observed after the heterogeneity was eliminated by excluding one study (OR = 1.15, 95% CI: 1.06–1.25, P_OR = 0.001, I² = 0%). This association was further identified by both subgroup analyses and a sensitivity analysis. Conclusions: This meta‐analysis suggests that the GSTT1 null genotype contributes to an increased colorectal cancer risk in the Asian population.